This COBRE renewal application is aimed at continuing the development of the Center for Colon Cancer Research (CCCR) at the University of South Carolina, in Columbia, SC. The CCCR is committed to research on the biology, prevention, and therapy of colorectal cancer. Adenocarcinomas of the colon and rectum are one of the most common cancers in the West. Each year in the US, there are approximately 155,000 newly diagnosed cases of colorectal cancer, and about 56,000 deaths, making the disease a leading cause of cancer in this country. In the ~4 years since inception of COBRE funding, the CCCR has made significant strides in enhancing the number of its independent scientists, as judged by: (i) establishment of fully functional laboratories staffed by students, postdoctoral fellows, and technicians;(ii) publishing results of research in highly regarded, peer-reviewed journals;(iii) applying for and winning extramural research grants;and (iv) attracting invitations to speak at conferences and seminars. The CCCR is now poised to move to the next level, and establish itself as a self-standing center that contributes to the nation's efforts in research on colorectal cancer. To do this, the current application proposes three primary aims: To carry out studies of specific molecular, biochemical, and genetic factors that affect the emergence and progression of colorectal cancer (Aim 1.);to provide Core facilities in support of these and future research efforts (Aim 2.);and to manage and oversee the administrative and outreach activities of the CCCR (Aim 3). In all, the proposed COBRE program will have two major long-term benefits. First, it will increase the number of independent and productive researchers that are competitive for NIH funding at the University of South Carolina. Second, it will generate a cohort of investigators focused on a biomedical problem of central importance to the NIH (i.e., that of colorectal cancer), thereby forging a multidisciplinary team that will be poised to apply for program project grant support (P01) from the NIH. In achieving these goals, the CCCR will enhance the University of South Carolina in its research, teaching, and service missions, and contribute to the NIH in its quest to improve national health.